Disseminated candidiasis is associated with an extremely poor prognosis. A critical step in both the initiation and the ongoing process of metastasis is detachment of a subpopulation of cells from foci of infection or contamination. The long term goal of this research is to understand the processes involved in mobilization of Candida albicans infective communities at the genetic, physiological and cellular levels. The central hypothesis is that 1 role of the yeast morphological form is to mobilize a portion of the microbial population by an active process that is orchestrated at the community level. The biofilm in vitro model provides an appropriate and tractable system for testing this hypothesis. The Specific Aims are: 1) to characterize clinically relevant physiological characteristics of the detached subpopulation. The working hypothesis is that the detached subpopulation will exhibit metabolic activity similar to cells that are not nutrient limited, but will exhibit cell wall properties that are functionally relevant to either survival as planktonic cells, or to seeding further biofilm communities. We will characterize susceptibility of the membrane to disruption by antimicrobial agents, metabolic activity and adhesion to relevant surfaces. The expected outcome is an understanding of the relationship between physiology and functional role of the detached subpopulation. 2) To identify genes that are most likely to be specifically involved in community mobilization. Transcript profiling will be used to determine levels of differential gene expression in the detached subpopulation with reference to a set of test cultures. Genes worthy of more detailed analysis will be selected based on analysis of a matrix of comparisons and putative functional relevance. The expected outcome is identification of a set of genes that are involved specifically in mobilization of C. albicans biofilm communities. This research will enhance U.S. healthcare by leading to novel strategies for containment of C. albicans infections. In addition to contributing to our fundamental understanding of functional specialization within C. albicans biofilm communities, it will provide the basis for development of methods for screening for adjuvant agents that will inhibit dissemination of these fungal infections. [unreadable] [unreadable] [unreadable]